The biggest drug merger in Massachusetts’ history is teed up and ready to go — as long as a hardy band of rebels doesn’t get in the way.

Takeda Pharmaceutical shareholders will vote Dec. 5 on whether to approve the Tokyo company’s nearly $62 billion purchase of Shire, known for its rare-disease treatments. It would be the largest Western acquisition ever made by a Japanese buyer, and would catapult Takeda into the ranks of the top 10 drug makers in the world.

Both players are based in other countries. But the potential impact in Massachusetts is considerable. While Shire is technically headquartered in Dublin, it has been largely run out of its main US campus in Lexington, and is the state’s second largest employer in the sector after Sanofi Genzyme. Takeda isn’t far behind in terms of local jobs, following its acquisitions of Ariad and Millennium (now together as part of Takeda’s oncology unit in Cambridge).

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Of course, cuts are inevitable with a deal like this. But Massachusetts could actually see a net increase in employment: Takeda plans to shutter its US headquarters outside Chicago, where about 940 people work, and move those operations to Greater Boston sometime after the Shire deal closes as anticipated on Jan. 8.

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First, Takeda needs to get past that shareholder meeting. A crew of dissidents, more than 100 strong, is trying to persuade other investors to join the cause. This group includes former Takeda employees and founding family members, most notably former company chairman Kunio Takeda. The Shire deal is too costly, they say, bringing with it too much debt. The critics point to Takeda’s poor stock performance since the deal’s announcement in May as evidence. They also worry that non-Japanese investors will have too much clout after the merger, investors that may not appreciate Takeda’s history and traditions.

The rebellion suffered a serious setback before Thanksgiving when influential advisory firms ISS and Glass Lewis came out in favor of the deal. They essentially said the dissidents’ concerns didn’t outweigh the corporate rationale behind the tie-up: The two companies’ drug pipelines and research work are complementary, and the projected annual cost savings of $1.4 billion-plus are considerable. These firms hold a lot of clout with big institutional investors, such as State Street and Wellington.

The rebels remain undeterred. They continued to make their case to individual shareholders in a last-ditch plea this week. The group has estimated that at least 15 percent of Takeda investors will vote against the deal, and more are coming on board. They need 34 percent of voting shares on their side to win. One hope: that some of the financial institutions involved with the deal as advisers and underwriters that also hold Takeda shares will relinquish their voting rights because of possible conflicts of interest.

Shire came into this marriage as a reluctant partner, initially rebuffing Takeda’s advances. Takeda was a relentless suitor, upping its price to seal the deal. When the managements of merger partners agree, it can be tough for unhappy shareholders to get in the way. But the outcome can’t be certain until the votes are counted.